Table 4Adverse events reported in randomized controlled trials of pegylated interferons for chronic hepatitis C infection

Study Trial Type HIV N Intervention Ribavirin daily dose Adverse Events
Silva 2006
Argentina, Mexico, Germany
COMPARE
H2H (early response)36Peginterferon alfa-2b
1.5 μg/kg
1× / week for 8 weeks
13 mg/kg dailyWithdrawals due to AE: 4/18 (22.22%)
Anemia: 10/18 (55.56%)
Flu-like symptoms: 5/18 (27.78%)
Neutropenia: 10/18 (55.56%)
Thrombocytopenia: 3/18 (16.67%)
Peginterferon alfa-2a
180 μg
1× / week for 8 weeks
13 mg/kg dailyWithdrawals due to AE: 2/18 (11.11%)
Anemia: 9/18 (50%)
Flu-like symptoms: 3/18 (16.67%)
Neutropenia: 12/18 (66.67%)
Thrombocytopenia: 5/18 (27.78%)
Sporea 2006
Romania
H2H (early response)116Peginterferon alfa-2a
180 μg/kg
1× / week for 12 weeks
800–1200 mg daily
Peginterferon alfa-2b
1.5 μg/kg
1× / week for 12 weeks
800–1200 mg daily
Alfaleh 2004
Saudi Arabia
PEG-IFN vs interferon96peginterferon alfa-2b
100 μg1× / week for 48 weeks
800 mg dailyWithdrawals due to AE: 3/48 (6.25%)
Anemia: 35/48 (72.92%)
Deaths: 0/48 (0%)
Depression: 4/48 (8.33%)
Dose reduction: 6/48 (12.5%)
Flu-like symptoms: 19/48 (39.58%)
Thrombocytopenia: 4/48 (8.33%)
Thyroid disease: 8/48 (16.67%)
Skin rash: 10/48 (20.83%)
interferon alfa-2b
3 million units
3× / week for 48 weeks
800 mg dailyWithdrawals due to AE: 1/48 (2.08%)
Anemia: 27/48 (56.25%)
Deaths: 1/48 (2.08%)
Depression: 3/48 (6.25%)
Dose reduction: 4/48 (8.33%)
Flu-like symptoms: 16/48 (33.33%)
Thrombocytopenia: 3/48 (6.25%)
Thyroid disease: 3/48 (6.25%)
Skin rash: 5/48 (10.42%)
Bruno 2004
Italy
PEG-IFN vs interferon311peginterferon alfa-2b
1×/week for 48 weeks
1000–1200 mg dailyWithdrawals due to AE: 20/163 (12.27%)
Dose reduction: 76/163 (46.63%)
Severe (grade 3 or 4) adverse events: 18/163 (11.04%)
interferon alfa-2b
6 million units every other day for 48 weeks
1000–1200 mg dailyWithdrawals due to AE: 38/148 (25.68%)
Dose reduction: 57/148 (38.51%)
Severe (grade 3 or 4) adverse events: 33/148 (22.3%)
Derbala 2005
Egypt
PEG-IFN vs interferon61Peginterferon alfa-2b
1.5 μg/kg
1× / week for 48 weeks
800–1200 mg dailyWithdrawals due to AE: 5/30 (16.67%)
Dose reduction: 9/30 (30%)
Flu-like symptoms: 30/30 (100%)
Interferon alfa-2b
3 million units
3× / week for 48 weeks
800–1200 mg dailyWithdrawals due to AE: 4/31 (12.9%)
Dose reduction: 7/31 (22.58%)
Flu-like symptoms: 31/31 (100%)
Lee 2005
Taiwan
PEG-IFN vs interferon153Peginterferon alpha-2b
1.5 μg/kg
1× / week for 24 weeks
1000–1200 mg dailyAnemia: 26/76 (34.21%)
Deaths: 1/76 (1.32%)
Dose reduction: 21/76 (27.63%)
Neutropenia: 17/76 (22.37%)
Thrombocytopenia: 20/76 (26.32%)
anxiety/depression: 21/76 (27.63%)
Interferon alpha-2b
3 million unit
3× / week for 24 weeks
1000–1200 mg dailyAnemia: 18/77 (23.38%)
Deaths: 0/77 (0%)
Dose reduction: 9/77 (11.69%)
Neutropenia: 5/77 (6.49%)
Thrombocytopenia: 8/77 (10.39%)
anxiety/depression: 10/77 (12.99%)
Mangia (A) 2005
Italy
PEG-IFN vs Interferon362Peginterferon alfa-2a (with amantadine)
180 μg
1× / week for 48 weeks
1000–1200 mg dailyFlu-like symptoms: 54/121 (44.63%)
Weight loss: 12/121 (9.92%)
Psychiatric symptoms: 15/121 (12.4%)
Interferon alpha-2a (with amantadine)
3 million unit
3× / week for 48 weeks
1000-1200 mg daiilyFlu-like symptoms: 60/120 (50%)
Weight loss: 6/120 (5%)
Psychiatric symptoms: 16/120 (13.33%)
Interferon alpha-2a
3 million unit
3× / week for 48 weeks
1000–1200 mg dailyFlu-like symptoms: 53/121 (43.8%)
Weight loss: 4/121 (3.31%)
Psychiatric symptoms: 20/121 (16.53%)
Manns 2001
Multiple (Europe, Canada, Argentina, US)
PEG-IFN vs interferon1530peginterferon alfa-2b(0.5 μg/kg)
0.5 μg/kg
1× / week for 48 weeks
1000–1200 mg dailyWithdrawals due to AE: 67/514 (13.04%)
Depression: 149/514 (28.99%)
Dose reduction: 185/514 (35.99%)
peginterferon alfa-2b (1.5 μg/kg)
1.5 ug/kg
1× / week for 48 weeks
800 mg dailyWithdrawals due to AE: 72/511 (14.09%)
Depression: 158/511 (30.92%)
Dose reduction: 215/511 (42.07%)
interferon 2b
3 mu
3× / week for 48 weeks
1000–1200 mg dailyWithdrawals due to AE: 66/505 (13.07%)
Depression: 172/505 (34.06%)
Dose reduction: 172/505 (34.06%)
Scotto 2005PEG-IFN vs interferon78Peginterferon alfa-2b
1.5 μg/kg
1× / week for 52 weeks
800–1200 mg dailyFlu-like symptoms: 15/26 (57.69%)
emotional disturbances, mainly depression: 8/26 (30.77%)
Interferon alfa-2b (3×/week)
6 million units
3× / week for 52 weeks
800–1200 mg dailyFlu-like symptoms: 18/26 (%)
emotional disturbances, mainly depression: 9/26 (%)
Interferon alfa-2b (daily)
3 million units daily for 52 weeks
800–1200 mg dailyFlu-like symptoms: 11/26 (42.31%)
emotional disturbances, mainly depression: 5/26 (19.23%)
Tsubota 2005
Japan
PEG-IFN vs interferon48Peginterferon alfa-2b
1.5 μg/kg
1× / week for 48 weeks
600–1000 mg daily
Interferon alfa-2b
6 million units
3× / week for 48 weeks
600–1000 mg daily
Arizcorreta 2004
Spain
PEG-IFN vs interferonHIV subgroup21peginterferon alfa-2a
180 μg
1× / week for 48 weeks
800 mg dailyWithdrawals due to AE: 2/11 (18.18%)
Interferon alfa-2a
3 million units
3× / week for 48 weeks
800 mg dailyWithdrawals due to AE: 2/10 (20%)
Carrat 2004
France
PEG-IFN vs interferonHIV subgroup412peginterferon alfa-2b
1.5 μg/kg
1× / week for 48 weeks
800 mg dailyWithdrawals due to AE: 33/205 (16.1%)
Anemia: 1/194 (0.52%)
Deaths: 5/194 (2.58%)
Depression: 46/194 (23.71%)
Dose reduction: 64/194 (32.99%)
Flu-like symptoms: 172/194 (88.66%)
Neutropenia: 14/194 (7.22%)
Thrombocytopenia: 9/194 (4.64%)
interferon alfa-2b
3 million units
3× / week for 48 weeks
800 mg dailyWithdrawals due to AE: 30/207 (14.49%)
Anemia: 1/189 (0.53%)
Deaths: 2/189 (1.06%)
Depression: 55/189 (29.1%)
Dose reduction: 39/189 (20.63%)
Flu-like symptoms: 151/189 (79.89%)
Neutropenia: 3/189 (1.59%)
Thrombocytopenia: 1/189 (0.53%)
Chung 2004
US
Adult AIDS Clinical Trials
Group A5071
PEG-IFN vs interferonHIV subgroup133peginterferon alfa-2a
180 μg
1× / week for 48 weeks
600–1000 mg dailyWithdrawals due to AE: 8/66 (12.12%)
Anemia: 3/66 (4.55%)
Depression: 9/66 (13.64%)
Flu-like symptoms: 39/66 (59.09%)
Neutropenia: 53/66 (80.3%)
Thrombocytopenia: 16/66 (24.24%)
Interferon alfa-2a
3-6 million iu
3× / week for 48 weeks
600–1000 mg dailyWithdrawals due to AE: 8/67 (11.94%)
Anemia: 1/67 (1.49%)
Depression: 8/67 (11.94%)
Flu-like symptoms: 38/67 (56.72%)
Neutropenia: 23/67 (34.33%)
Thrombocytopenia: 2/67 (2.99%)
Crespo 2007
Spain
PEG-IFN vs interferonHIV subgroup121Peginterferon alfa-2b
1.5 μg/kg
1× / week for 24–48 weeks
800 mg dailyWithdrawals due to AE: 6/60 (10%)
Deaths: 0/60 (0%)
Dose reduction: 16/60 (%)
Flu-like symptoms: 53/60 (88.33%)
Interferon alfa-2b
3 million units
3× / week for 24–48 weeks
800 mg dailyWithdrawals due to AE: 7/61 (11.48%)
Deaths: 2/61 (3.28%)
Dose reduction: 0/61 (0%)
Flu-like symptoms: 49/61 (80.33%)
Laguno 2004
Spain
PEG-IFN vs interferonHIV subgroup95Peginterferon alpha-2b
100–150 μg
1× / week for 48 weeks
800–1200 mg dailyWithdrawals due to AE: 9/52 (17.31%)
Anemia: 16/52 (30.77%)
Depression: 19/52 (36.54%)
Dose reduction: 22/52 (42.31%)
Flu-like symptoms: 46/52 (88.46%)
Neutropenia: 14/52 (26.92%)
Thrombocytopenia: 13/52 (25%)
Interferon alpha-2b
3 million units
3× / week for 48 weeks
800–1200 mg dailyWithdrawals due to AE: 5/43 (11.63%)
Anemia: 10/43 (23.26%)
Depression: 22/43 (51.16%)
Dose reduction: 16/43 (37.21%)
Flu-like symptoms: 32/43 (74.42%)
Neutropenia: 7/43 (16.28%)
Thrombocytopenia: 6/43 (13.95%)
Poizot-Martin 2003
France
PEG-IFN vs interferonHIV subgroup62Peginterferon alfa-2b
180 μg
1× / week for 6–12 Months
1600 mg daily
Interferon alfa-2b
3 million units
3× / week for 6–12 Months
1600 mg daily
Torriani 2004
Multiple APRICOT
PEG-IFN vs interferonHIV subgroup860Peginterferon alfa-2a
180 μg
1× / week for 48 weeks
800 mg dailyWithdrawals due to AE: 34/290 (11.72%)
Anemia: 6/288 (2.08%)
Depression: 76/288 (26.39%)
Thrombocytopenia: 1/288 (0.35%)
Dose reduction due to adverse event: 30/288 (10.42%)
Dose reduction due to laboratory abnormality: 97/288 (33.68%)
Peginterferon alfa-2a (no ribavirin)
180 ug
1× / week for 48 weeks
Withdrawals due to AE: 34/289 (11.76%)
Anemia: 6/286 (2.1%)
Depression: 57/286 (19.93%)
Thrombocytopenia: 4/286 (1.4%) Dose reduction due to adverse event: 21/286 (7.34%)
Dose reduction due to laboratory abnormality (anemia, neutropenia, thrombocytopenia, other): 94/286 (32.87%)
Interferon alfa-2a
3 million units
3× / week for 48 weeks
800 mg dailyWithdrawals due to AE: 41/289 (14.19%)
Anemia: 3/285 (1.05%)
Depression: 64/285 (22.46%)
Thrombocytopenia: 0/286 (0%)
Dose reduction due to adverse event: 33/285 (11.58%)
Dose reduction due to laboratory abnormality (anemia, neutropenia, thrombocytopenia, other): 18/285 (6.32%)
Fried 2002
Multiple (US, Europe, Australia, Brazil)
Pegasys International Study Group
PEG-IFN + ribavirin vs PEG-IFN monotherapy1121Peginterferon alfa-2a
180 μg
1× / week for 48 weeks
1000–1200 mg dailyWithdrawals due to AE: 32/453 (7.06%)
Depression: 100/451 (22.17%)
Dose reduction for adverse event: 48/451 (10.64%)
Dose reduction for laboratory abnormality (anemia, neutropenia, thrombocytopenia): 111/451 (24.61%)
Interferon alfa-2b
3 million unit
3× / week for 48 weeks
1000–1200 mg dailyWithdrawals due to AE: 43/444 (9.68%)
Deaths: 1/444 (0.23%)
Depression: 134/443 (30.25%) Dose reduction for adverse event: 47/443 (10.61%)
Dose reduction for laboratory abnormality (anemia, neutropenia, thrombocytopenia): 36/443 (8.13%)
Peginterferon alfa-2a (no ribavirin)
180 μg
1× / week for 48 weeks
Withdrawals due to AE: 13/224 (5.8%)
Depression: 45/223 (20.18%)
Dose reduction for adverse event: 14/223 (6.28%)
Dose reduction for laboratory abnormality (anemia, neutropenia, thrombocytopenia): 54/223 (24.22%)
Inati 2005
Lebanon
PEG-IFN + ribavirin vs PEG-IFN monotherapy20Peginterferon alfa-2a (plus placebo)
180 μg
1× / week for 48 weeks
Peginterferon alfa-2a (plus ribavirin)
180 μg
1× / week for 48 weeks
10.6 mg/kg daily
Kamal (A) 2002
Germany
PEG-IFN + ribavirin vs PEG-IFN monotherapy42Peginterferon alfa-2a
180 μg
1× / week for 48 weeks
800–1200 mg daily
Peginterferon alfa-2a
180 μg
1× / week for 48 weeks
Interferon alfa-2a
3–6 million units
3× / week for 48 weeks
Cargnel 2005
Italy
Italian Co-infection Study (ICOS)
PEG-IFN + ribavirin vs PEG-IFN monotherapyHIV subgroup135Peginterferon alfa-2b (plus ribavirin)
1.5 μg/kg
1× / week for 48 weeks
800 mg dailyWithdrawals due to AE: 15/69 (21.74%)
Dose reduction: 12/69 (17.39%)
Flu-like symptoms: 15/69 (21.74%)
Psychiatric disorders: 4/69 (5.8%)
Hematological toxicity: 13/69 (18.84%)
Peginterferon alfa-2b
monotherapy
1.5 μg/kg
1× / week for 48 weeks
Withdrawals due to AE: 15/66 (22.73%)
Dose reduction: 8/66 (12.12%)
Flu-like symptoms: 2/66 (3.03%)
Psychiatric disorders: 3/66 (4.55%)
Hematological toxicity: 10/66 (15.15%)
Khalili 2005
US
PEG-IFN + ribavirin vs PEG-IFN monotherapyHIV subgroup154Peginterferon alfa-2a (plus ribavirin)
180 mg
1× / week for 48 weeks
800 mg dailyDepression: 6/37 (16.22%)
Neutropenia: 2/37 (5.41%)
Peginterferon alfa-2a (plus placebo)
180 mg
1× / week for 48 weeks
Depression: 7/39 (17.95%)
Neutropenia: 1/39 (2.56%)

From: Evidence Tables

Cover of Drug Class Review: Pegylated Interferons for Chronic Hepatitis C Infection
Drug Class Review: Pegylated Interferons for Chronic Hepatitis C Infection: Final Report [Internet].
Chou R, Carson S, Chan BKS, et al.
Portland (OR): Oregon Health & Science University; 2007 May.
Copyright © 2007, Oregon Health & Science University, Portland, Oregon.

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